Blood pressures, heart rate and locomotor activity during salt loading and angiotensin II infusion in protease-activated receptor 2 (PAR2) knockout mice.
BACKGROUND
In this study we used radiotelemetry to measure hemodynamic variables and locomotor activity in conscious unrestrained male Protease-Activated Receptor 2 (PAR-2) knockout mice in order to provide a detailed assessment of their blood pressure phenotype. In addition we tested for an influence of PAR-2 on salt-sensitivity (8% versus 0.5% NaCl diet, 2.5 weeks) and angiotensin II-induced hypertension (1 microg Ile5-angiotensin II/kg/min versus 0.25 microl/h saline, 2 weeks).


RESULTS
Systolic arterial pressures of PAR-2 -/- (129 +/- 1 mmHg, n = 21, P < 0.05) were statistically higher than those of C57BL/6J (124 +/- 1 mmHg, n = 33) throughout the 24 h period under baseline conditions. Pulse pressures in PAR-2 -/- were also significantly elevated (33 +/- 1 mmHg versus 30 +/- 1 mmHg, P < 0.05), whereas diastolic arterial pressures were not. Heart rates in PAR-2 -/- were not significantly different than controls, with the exception that heart rate of PAR-2 -/- was 23 beats per min higher than controls (P < 0.001) during periods of nocturnal activity. The diurnal pattern and intensity of locomotor activity were not found to differ between strains. A high salt diet led to increased blood pressures, decreased heart rates, increased time spent active and decreased intensity levels of locomotor activity. Salt-induced changes in systolic and pulse pressures in PAR-2 -/- were less than in C57B/6J. Angiotensin II treatment increased pressures, decreased heart rates, decreased time spent active and decreased intensity levels of activity of PAR-2 -/-, all to the same extent as C57BL/6J. A trend of lower blood pressures during the middle period of angiotensin II treatment period was observed in individual PAR-2 -/-.


CONCLUSIONS
The data indicated gene knockout of PAR-2 was associated with a modest change in blood pressure phenotype. PAR-2 -/- mice exhibited moderate elevation of systolic arterial and pulse pressures, yet no increased diastolic arterial pressure, no increased blood pressure responses to high salt diet and a subtle difference in the time course of the blood pressure responses to angiotensin II infusion.
McGuire
John J
JJ
Cardiovascular Research Group, Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada. mcguire@mun.ca
Van Vliet
Bruce N
BN
Halfyard
Sarah J
SJ
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D044464:Receptor, PAR-2 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D044464:Receptor, PAR-2; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II